Modafinil improves real driving performance in patients with hypersomnia: a randomized double-blind placebo-controlled crossover clinical trial

Abstract

Study objective: Patients with excessive daytime sleepiness (EDS) are at high risk for driving accidents, and physicians are concerned by the effect of alerting drugs on driving skills of sleepy patients. No study has up to now investigated the effect of modafinil (a reference drug to treat EDS in patients with hypersomnia) on on-road driving performance of patients suffering from central hypersomnia. The objective is to evaluate in patients with central hypersomnia the effect of a wake-promoting drug on real driving performance and to assess the relationship between objective sleepiness and driving performance.

Design and participants: Randomized, crossover, double-blind placebo-controlled trial conducted among 13 patients with narcolepsy and 14 patients with idiopathic hypersomnia. Patients were randomly assigned to receive modafinil (400 mg) or placebo for 5 days prior to the driving test. Each condition was separated by at least 3 weeks of washout.

Measurements: Mean number of Inappropriate Line Crossings, Standard Deviation of Lateral Position of the vehicle and mean sleep latency in the Maintenance of Wakefulness Test were assessed.

Results: Modafinil reduced the mean number of Inappropriate Line Crossings and Standard Deviation of Lateral Position of the vehicle compared to placebo (F(1,25) = 4.88, P < 0.05 and F(1,25) = 3.87, P = 0.06 tendency). Mean sleep latency at the Maintenance of Wakefulness Test significantly correlated with the mean number of Inappropriate Line Crossings (r = -0.41, P < 0.001).

Conclusions: Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia. The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population.

Keywords: Automobile driving; MWT; idiopathic hypersomnia; modafinil; narcolepsy; sleepiness.

Figure 1

Overview of protocol design. A placebo condition (top panel) and a modafinil condition (400 mg/day) (lower panel) for 5 consecutive days separated by a 3-week washout period were administered in a randomized crossover double-blind placebo-controlled design in patients with narcolepsy and idiopathic hypersomnia (IH). The length of the 3-day period at home was chosen due to the half-life of modafinil (15 h); 3 days are required to eliminate the drug. Treatment was administrated at 08:00 (modafinil 2×100 mg) and 12:30 (modafinil 2×100 mg). In each condition, a period of 3 days at home with actigraphic recordings and sleep diary was followed by successive 36 h with 2 polysomnography (PSG) nights (nights 4 and 5) and 2 days to perform a 4 × 40-min Maintenance of Wakefulness Test (MWT) (day 4) and a 2-h on-road driving session (day 5).

Figure 2

Schematic representation of the on-road driving test. A Continental system continuously records the actual position of the car within the traffic lane by tracking the relative distance of the car from the delineated stripe in the right of the road. Primary outcomes are Inappropriate Line Crossings (ILC) and Standard Deviation of Lateral Position (SDLP) (cm).

Figure 3

Mean number of Inappropriate Line Crossings (ILC) with on-road driving in patients with narcolepsy and idiopathic hypersomnia (IH) under placebo and modafinil and in healthy controls (mean ± standard error). *P < 0.05.